HSD17B2

{{Short description|Protein-coding gene in the species Homo sapiens}}

17β-Hydroxysteroid dehydrogenase 2 (17β-HSD2) is an enzyme of the 17β-hydroxysteroid dehydrogenase (17β-HSD) family that in humans is encoded by the HSD17B2 gene.{{cite journal | vauthors = Durocher F, Morissette J, Labrie Y, Labrie F, Simard J | title = Mapping of the HSD17B2 gene encoding type II 17 beta-hydroxysteroid dehydrogenase close to D16S422 on chromosome 16q24.1-q24.2 | journal = Genomics | volume = 25 | issue = 3 | pages = 724–6 | date = Feb 1995 | pmid = 7759109 | doi = 10.1016/0888-7543(95)80017-G }}{{cite journal | vauthors = Persson B, Kallberg Y, Bray JE, Bruford E, Dellaporta SL, Favia AD, Duarte RG, Jörnvall H, Kavanagh KL, Kedishvili N, Kisiela M, Maser E, Mindnich R, Orchard S, Penning TM, Thornton JM, Adamski J, Oppermann U | title = The SDR (short-chain dehydrogenase/reductase and related enzymes) nomenclature initiative | journal = Chemico-Biological Interactions | volume = 178 | issue = 1–3 | pages = 94–8 | date = Mar 2009 | pmid = 19027726 | pmc = 2896744 | doi = 10.1016/j.cbi.2008.10.040 | bibcode = 2009CBI...178...94P }}{{cite web | title = Entrez Gene: HSD17B2 hydroxysteroid (17-beta) dehydrogenase 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3294}}

Function

17β-HSD2 is involved in inactivation of androgens and estrogens,{{cite journal | vauthors = Moeller G, Adamski J | title = Multifunctionality of human 17beta-hydroxysteroid dehydrogenases | journal = Mol. Cell. Endocrinol. | volume = 248 | issue = 1–2 | pages = 47–55 | year = 2006 | pmid = 16413960 | doi = 10.1016/j.mce.2005.11.031 | s2cid = 54235551 | quote = 17β-HSD types 1–3, the key enzymes in homeostasis of steroid hormones (Andersson, 1995, Blomquist, 1995) seem to have their role solely in steroid metabolism catalysing reactions on steroid substrates only. [...] 17β-HSD2, an enzyme with broad tissue distribution (Casey et al., 1994), plays its major role in the inactivation of potent steroid hormones oxidising estradiol and testosterone to estrone and androstenedione, respectively (Wu et al., 1993). Beside this, 17β-oxidation of intermediates of steroid metabolism, e.g. 5α-androstane-3α,17β-diol, dihydrotestosterone and Δ5-androstene-3β,17β-diol is described (for review see Mindnich et al. (2004b). Additionally, human 17β-HSD type 2 has high 20α-HSD activity with progestins (Puranen et al., 1999).}} being accurately describable as "antiandrogenic" and "antiestrogenic",{{cite journal | vauthors = Wang CT, Li CF, Wu WJ, Huang CN, Li CC, Li WM, Chan TC, Liang PI, Hsing CH, Liao KM | title = High Expression of 17β-hydroxysteroid Dehydrogenase Type 2 is Associated with a Better Prognosis in Urothelial Carcinoma of the Urinary Tract | journal = Journal of Cancer | volume = 7 | issue = 15 | pages = 2221–2230 | year = 2016 | pmid = 27994658 | pmc = 5166531 | doi = 10.7150/jca.16777 | quote = "HSD17B2 has both anti-estrogenic and anti-androgenic functions." }} and is the key 17β-HSD isozyme in androgen and estrogen inactivation.{{Additional citation needed|date=July 2017}} Specific reactions catalyzed by 17β-HSD2 include estradiol to estrone, testosterone to androstenedione, and androstenediol to {{abbrlink|DHEA|dehydroepiandrosterone}}.{{cite journal | vauthors = Mindnich R, Möller G, Adamski J | title = The role of 17 beta-hydroxysteroid dehydrogenases | journal = Mol. Cell. Endocrinol. | volume = 218 | issue = 1–2 | pages = 7–20 | year = 2004 | pmid = 15130507 | doi = 10.1016/j.mce.2003.12.006 | s2cid = 26877571 }} In addition to 17β-HSD activity, this enzyme also shows high 20α-hydroxysteroid dehydrogenase activity and can activate the weak progestogen 20α-hydroxyprogesterone into the potent progestogen progesterone.

Expression

17β-HSD2 is widely expressed throughout the body including in the placenta, liver, intestines, endometrium, kidney, pancreas, breast, prostate, bone, and many other tissues.{{cite journal | vauthors = Hilborn E, Stål O, Jansson A | title = Estrogen and androgen-converting enzymes 17β-hydroxysteroid dehydrogenase and their involvement in cancer: with a special focus on 17β-hydroxysteroid dehydrogenase type 1, 2, and breast cancer | journal = Oncotarget | volume = 8 | issue = 18 | pages = 30552–30562 | date = May 2017 | pmid = 28430630 | pmc = 5444764 | doi = 10.18632/oncotarget.15547 }}{{cite book | title = Hormones, Brain and Behavior| chapter-url = https://books.google.com/books?id=NT8oCwAAQBAJ&pg=RA3-PA69 | date = 9 November 2016 | publisher = Elsevier Science | isbn = 978-0-12-803608-2 |pages = 69 | volume = 4: Clinical Important Effects of Hormones on Brain and Behavior | editor-first1 = Stafford | editor-last1 = Lightman | chapter = 4.02: Disorders of Sexual Development in Males: Molecular Genetics, Epigenetics, Gender Identity, and Cognition | first1 = Yuan-Shan | last1 = Zhu | first2 = Julianne L. | last2 = Imperato-McGinley }}

Clinical significance

Polymorphisms in HSD17B2 have been associated with breast cancer and prostate cancer.{{cite journal | vauthors = Moeller G, Adamski J | title = Integrated view on 17beta-hydroxysteroid dehydrogenases | journal = Mol. Cell. Endocrinol. | volume = 301 | issue = 1–2 | pages = 7–19 | year = 2009 | pmid = 19027824 | doi = 10.1016/j.mce.2008.10.040 | s2cid = 30321495 }} 17β-HSD2 activity has also been associated with endometriosis and osteoporosis,{{cite journal | vauthors = Bulun SE, Cheng YH, Pavone ME, Yin P, Imir G, Utsunomiya H, Thung S, Xue Q, Marsh EE, Tokunaga H, Ishikawa H, Kurita T, Su EJ | title = 17Beta-hydroxysteroid dehydrogenase-2 deficiency and progesterone resistance in endometriosis | journal = Semin. Reprod. Med. | volume = 28 | issue = 1 | pages = 44–50 | year = 2010 | pmid = 20108182 | pmc = 4511594 | doi = 10.1055/s-0029-1242992 }} and inhibitors of the enzyme are of potential interest in the treatment of the latter condition.{{cite journal | vauthors = Marchais-Oberwinkler S, Henn C, Möller G, Klein T, Negri M, Oster A, Spadaro A, Werth R, Wetzel M, Xu K, Frotscher M, Hartmann RW, Adamski J | title = 17β-Hydroxysteroid dehydrogenases (17β-HSDs) as therapeutic targets: protein structures, functions, and recent progress in inhibitor development | journal = J. Steroid Biochem. Mol. Biol. | volume = 125 | issue = 1–2 | pages = 66–82 | year = 2011 | pmid = 21193039 | doi = 10.1016/j.jsbmb.2010.12.013 | s2cid = 23767100 }}{{cite journal | vauthors = Soubhye J, Alard IC, van Antwerpen P, Dufrasne F | title = Type 2 17-β hydroxysteroid dehydrogenase as a novel target for the treatment of osteoporosis | journal = Future Med Chem | volume = 7 | issue = 11 | pages = 1431–56 | year = 2015 | pmid = 26230882 | doi = 10.4155/fmc.15.74 }} Inactivating mutations resulting in a syndrome of congenital deficiency of 17β-HSD2 have not been reported to date.{{cite book|author=J. Larry Jameson|title=Principles of Molecular Medicine|url=https://books.google.com/books?id=UhjyBwAAQBAJ&pg=PA549|date=13 July 1998|publisher=Springer Science & Business Media|isbn=978-1-59259-726-0|pages=549–}}

HSD17B2

Function

Expression

Clinical significance

References

Further reading